Agomelatine, N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide, is a melatonin receptor agonist, and is a new antidepressant and antianxiety drug. EP0447285 discloses the chemical structure of agomelatine, and the use of agomelatine as an antianxiety drug, an antidepressant, and an antipsychotic drug. Agomelatine has a chemical structure represented by formula (I).

A number of methods for the synthesis of agomelatine have been reported, and they can generally be divided into two types, which both use 7-methoxy-1-tetralone as a starting material. The first type of methods are described in the literatures such as EP0447285, 1992. JMC, and 1994. JMC. (see reaction scheme I).

The disadvantages of this type of methods lie in that many steps are involved; the reaction in the first step is found to be poorly reproducible; compound (B) often goes through an incomplete aromatization in step (2) and the reactions in the subsequent steps do not usually go to complete either; purification of the mixture obtained in the saponification of step (3) is so difficult that column chromatography is necessitated; the hydrogenation pressure in step (7) is as high as 300 atm, as reported in the relevant patents, and it is difficult to generate such a high pressure in the industrial production; and the average total yield is lower than 30%.
The second type of methods are described in the literatures such as US2005/0182276 and Synthetic Communication 2001, 31(4), 321-629 (see reaction scheme II).

The advantages of this type of methods lie in that two carbon atoms and one nitrogen atom of the target molecule are introduced in the first step, and transformed into a target functional group through hydrogenation, which is desirable from an economic viewpoint; the intermediates can be readily separated and purified, and a single recrystallization gives the target product with a purity of 99%. However, the methods have the disadvantage that the hydrogenation of a cyano group also requires a high pressure of 300 atm, which is difficult to be generated in the industrial production.
Furthermore, 7-methoxy-1-tetralone used in those two types of methods as the starting material, is costly and not easily available.
In view of the above problems occurred in those methods for the synthesis of agomelatine, there remains a need for a new process for the manufacture of agomelatine, which uses easily available and inexpensive materials, is convenient and simple, and can be easily performed on an industrial scale.